IKK2: A Central Player in Allergic Reactions

Methods of identifying IKK2 activators or inhibitors for regulation of mast cell degranulation

Allergic diseases, such as atropic rhinitis, asthma, and atropic dermatitis are modulated mainly by mast cells. Cross-linking of the high affinity receptor for IgE on these cells activates intracellular signaling pathways that lead to degranulation and the release of histamine and other preformed chemical mediators. Most of the currently used anti-allergic drugs are inhibitors of these mediators because these bioactive mediators are thought to lead to allergic inflammation. However, existing anti-allergic drugs have an insufficient therapeutic effect on disease.

Recently, we have discovered the importance of IKK2 in early phase allergic reactions. IKK2 in mast cells mediates IgE-induced degranulation by phosphorylating SNAP-23 in an NF-kB-independent manner, leading to anaphylactic reactions. This suggests that molecules or biologics that inhibit IKK2 would be excellent therapeutic agents for anaphylactic reactions.